Difference between revisions of "Serotonin syndrome"

(Added info on MAOIs)
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===Causative Agents===
===Causative Agents===
*MAOIs (have long duration of action a ‘washout’ period of at least two weeks should be instituted before starting a SSRI)
*Drugs of Abuse: Cocaine, Ecstasy, Marijuana, Meth
*Drugs of Abuse: Cocaine, Ecstasy, Marijuana, Meth

Revision as of 16:31, 22 December 2015


  • Can be produced by any serotonergic medication
  • Vast majority of cases occur within therapeutic dosages and often from exposure to several different serotonergic drugs that increase CNS serotonin activity simultaneously, like while switching between antidepressant classes or drugs.
  • Most common cause of death is severe hyperthermia
  • According to one study, the most commonly reported cause of serotonin syndrome was ingestion of foods large in L-Tryptophan, precursor of serotonin, along with MAOI, while the second most common cause was ingestion of SSRI and MAOI.[1]

Causative Agents

  • SSRIs
  • MAOIs (have long duration of action a ‘washout’ period of at least two weeks should be instituted before starting a SSRI)
  • TCAs
  • Drugs of Abuse: Cocaine, Ecstasy, Marijuana, Meth
  • Analgesics: Demerol, fentanyl
  • Antiemetics
  • Triptans
  • Bromocriptine
  • OTC: Cough meds like Dextromethorphan, herbal products, St John’s Wort

Clinical Features

  • Altered mental status: Agitated delirium
  • Autonomic Instability: Hyperthermia, Tachycardia, hypertension, diaphoresis [2]
    • Often labile blood pressure, HR
  • Neuromuscular Abnormalities: Myoclonus, ocular clonus, rigidity, hyperreflexia, tremor
    • More pronounced in the lower extremities
    • Myoclonus: most common finding
      • Important to identify because it does not occur in other conditions that mimic serotonin syndrome

Differential Diagnosis

Altered mental status and fever


Hunter Toxicity Criteria Decision Rules

Serotonergic agent plus 1 of the following[3]:

  • Spontaneous clonus
  • Inducible clonus AND (agitation or diaphoresis)
  • Ocular Clonus AND (agitation or diaphoresis)
  • Tremor AND hyperreflexia
  • Hypertonia AND temp >38 AND (ocular clonus or inducible clonus)

84% Sn, 97% Sp


  • Discontinue all serotonergic drugs
  • Aggressive supportive care
    • If pressors required, direct acting (e.g. norepi, epi) preferred, MAO inhibition causes erratic response to dopamine
  • Benzos
    • Goal is to eliminate agitation, neuromuscular abnormalities, elevations in HR/BP
  • Cyproheptadine[4]
    • Give if benzos and supportive care fail to improve agitation and abnormal vitals
    • Serotonin antagonist
    • Give 12mg PO/NG; repeat with 2mg q2hr until clinical response is seen (max 32mg/d)
    • Give 4mg q6hr x48hr if pt is responsive to initial dose
  • Chlorpromazine[5]
    • Phenothiazine with antiserotonergic effects
    • 50mg to 100mg IM
    • Can consider in severe cases
  • Dexmedetomidine[6]
    • Small case series found this helpful in adolescent cases refractory to benzos
  • Treat hyperthermia
    • Hyperthermia due to increase in muscular activity, not change in set point
    • Intubate and paralyze if temp > 41.1
    • Standard cooling measures


  • Discharge mild cases with symptomatic treatment
  • 24hr admission for AMS or abnormal vital signs requiring further supportive care
  • Severe cases may require intubation and ventilation in ICU

See Also


  1. Stork CM. Serotonin Reuptake Inhibitors and Atypical Antidepressants. In: Flomenbaum N, Goldfrank L, Hoffman R, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies. 8th Ed. New York, NY: McGraw-Hill; 2006: 1070-1082
  2. Boyer, E. W. and Shannon, M. (2005) ‘The Serotonin Syndrome’, New England Journal of Medicine, 352(11), pp. 1112–1120. doi: 10.1056/nejmra041867
  3. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003;96:635-642
  4. Graudins, A., Stearman, A. and Chan, B. (1998) ‘Treatment of the serotonin syndrome with cyproheptadine’, The Journal of Emergency Medicine, 16(4), pp. 615–619. doi: 10.1016/s0736-4679(98)00057-2
  5. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100-109
  6. Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome. Ann Pharmacother. 2014; 48(12):1651-1654.